This K02 re-submission seeks salary support for Mehmet Sofuoglu, M.D., Ph.D. The candidate has a Ph.D. in pharmacology and has developed expertise in behavioral pharmacology including intravenous challenge studies with cocaine and nicotine in humans. He is currently an Associate Professor of Psychiatry at the Yale University School of Medicine. Dr. Sofuoglu has built an innovative research program on development of novel pharmacological treatments for cocaine and nicotine addiction. He has established a strong publication record, national recognition, and independent funding for his work in nicotine and cocaine addiction. His main research interests are: 1) neurobiological mechanisms of sex and menstrual cycle effects on stimulant addiction and 2) the GABA and adrenergic system as targets for the pharmacotherapy of stimulant addiction. During the next 5 years, the candidate will focus on two R01 projects. The first project, "GABA Medications and Tobacco Addiction" is a human laboratory study and will examine the dose-dependent effects of GABA enhancing medication tiagabine on smoking behavior, tobacco withdrawal severity, and craving for cigarettes in male and female smokers. The second project "Cocaine Withdrawal and Pharmacotherapy Response" is an outpatient clinical trial and will evaluate the efficacy of a beta- and alpha- adrenergic blocker, carvedilol for pharmacotherapy of cocaine addiction. Both these projects are consistent with the candidate's long-term research interest in medications development for addictive disorders. The candidate is seeking a K02 award to receive further training and gain expertise in other fields that will further expand his research scope including neurobiology of sex hormones and neurosteroids, and clinical trials methodology. To reach these training goals, the candidate proposes an educational program including coursework and mentoring from senior colleagues with relevant expertise. This K02 application will provide support for the candidate's sustained research in areas of cocaine and nicotine addiction. [unreadable] [unreadable] [unreadable]